7 results on '"Gomes, Antoniel Augusto Severo"'
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2. Allosteric modulation of ghrelin receptor signaling by lipids
- Author
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Damian, Marjorie, Louet, Maxime, Gomes, Antoniel Augusto Severo, M’Kadmi, Céline, Denoyelle, Séverine, Cantel, Sonia, Mary, Sophie, Bisch, Paulo M., Fehrentz, Jean-Alain, Catoire, Laurent J., Floquet, Nicolas, and Banères, Jean-Louis
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- 2021
- Full Text
- View/download PDF
3. The Neurospora crassa PCL-1 cyclin is a PHO85-1 (PGOV) kinase partner that directs the complex to glycogen metabolism and is involved in calcium metabolism regulation
- Author
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Campanella, Jonatas Erick Maimoni, primary, Candido, Thiago de Souza, additional, Barbosa, Luiz Carlos Bertucci, additional, Gomes, Antoniel Augusto Severo, additional, Leite, Carla Andréa, additional, Higashi, Erika Silva, additional, Barbugli, Paula Aboud, additional, Fontes, Marcos Roberto de Matos, additional, and Bertolini, Maria Célia, additional
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- 2022
- Full Text
- View/download PDF
4. Allosteric modulation of ghrelin receptor signaling by lipids
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Louet, Maxime, Casiraghi, Marina, Damian, Marjorie, Costa, Mauricio GS, Renault, Pedro, Gomes, Antoniel AS, Batista, Paulo, M'Kadmi, Céline, Mary, Sophie, Cantel, Sonia, Denoyelle, Severine, Ben Haj Salah, Khoubaib, Perahia, David, Bisch, Paulo, Fehrentz, Jean-Alain, Catoire, Laurent, Floquet, Nicolas, Banères, Jean-Louis, Mustafá, Emilio, Cordisco González, Santiago, Wagner, Renaud, Schiöth, Helgi, Perelló, Mario, Raingo, Jesica, Gomes, Antoniel Augusto Severo, M’Kadmi, Céline, Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Universidade Federal do Rio de Janeiro (UFRJ), Laboratoire de biologie physico-chimique des protéines membranaires (LBPC-PM (UMR_7099)), Institut de biologie physico-chimique (IBPC (FR_550)), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), ANR-17-CE11-0011,allosig,allostérie, dynamique conformationnelle et signalisation via les RCPG(2017), ANR-17-CE18-0022,GHScReen2,Biosenseurs originaux pour le criblage des ligands des Récepteurs Couplés aux Protéines G. Application au récepteur de la ghréline.(2017), and Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
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Phosphatidylinositol 4,5-Diphosphate ,MESH: Signal Transduction ,MESH: Fluorescence Resonance Energy Transfer ,Protein Conformation ,Lipid Bilayers ,General Physics and Astronomy ,MESH: Allosteric Regulation ,MESH: Receptors, Ghrelin ,MESH: Protein Conformation ,0302 clinical medicine ,Fluorescence Resonance Energy Transfer ,Receptors, Ghrelin ,Receptor ,MESH: Lipid Metabolism ,0303 health sciences ,Multidisciplinary ,Chemistry ,MESH: Lipid Bilayers ,digestive, oral, and skin physiology ,MESH: G(M3) Ganglioside ,Lipids ,MESH: Phosphatidylinositol 4,5-Diphosphate ,[SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics ,Membrane ,Ghrelin ,lipids (amino acids, peptides, and proteins) ,medicine.symptom ,Intracellular ,Signal Transduction ,Biophysical chemistry ,MESH: Mutation ,G protein ,Science ,Allosteric regulation ,Mechanism of action ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Allosteric Regulation ,medicine ,G(M3) Ganglioside ,Humans ,Cysteine ,[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM] ,030304 developmental biology ,Binding Sites ,MESH: Humans ,Cell Membrane ,General Chemistry ,MESH: Cysteine ,Lipid Metabolism ,MESH: Lipids ,MESH: Binding Sites ,Mutation ,Biophysics ,030217 neurology & neurosurgery ,MESH: Cell Membrane - Abstract
The membrane is an integral component of the G protein-coupled receptor signaling machinery. Here we demonstrate that lipids regulate the signaling efficacy and selectivity of the ghrelin receptor GHSR through specific interactions and bulk effects. We find that PIP2 shifts the conformational equilibrium of GHSR away from its inactive state, favoring basal and agonist-induced G protein activation. This occurs because of a preferential binding of PIP2 to specific intracellular sites in the receptor active state. Another lipid, GM3, also binds GHSR and favors G protein activation, but mostly in a ghrelin-dependent manner. Finally, we find that not only selective interactions but also the thickness of the bilayer reshapes the conformational repertoire of GHSR, with direct consequences on G protein selectivity. Taken together, this data illuminates the multifaceted role of the membrane components as allosteric modulators of how ghrelin signal could be propagated., The membrane is an integral component of the G protein-coupled receptor signaling machinery. Here authors demonstrate that lipids regulate the signaling efficacy and selectivity of the ghrelin receptor GHSR through specific interactions and bulk effects and observe PIP2 and GM3 induced shifts of the conformational equilibrium of GHSR away from its inactive state.
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- 2021
5. Molecular study of bothropstoxin-I, a myotoxin from Bothrops jararacussu: dynamical study of its conformational space
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Gomes, Antoniel Augusto Severo, Universidade Estadual Paulista (Unesp), Fontes, Marcos Roberto de Mattos, and Magro, Angelo José
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Snake venom ,PLA2s-homólogas ,MD ,Veneno de serpente ,Normal modes ,PLA2s-homologous ,Bothropstoxina-I ,Modos normais - Abstract
Submitted by Antoniel Augusto Severo Gomes (antoniel.gomes@unesp.br) on 2019-09-26T21:04:00Z No. of bitstreams: 2 Antoniel_A._S._Gomes-Tese-BGA-Parcial.pdf: 8330449 bytes, checksum: 3ccdb57c312dca93aff96b40f534e93d (MD5) Antoniel_A._S._Gomes-Tese-BGA.pdf: 53301098 bytes, checksum: 79735538110bf31ff1fb985ba2cd5bfe (MD5) Approved for entry into archive by ROSANGELA APARECIDA LOBO null (rosangelalobo@btu.unesp.br) on 2019-09-30T13:44:32Z (GMT) No. of bitstreams: 1 gomes_aas_dr_bot_par.pdf: 53163720 bytes, checksum: 37484200626ab49924f0b9a1423b9c71 (MD5) Made available in DSpace on 2019-09-30T13:44:32Z (GMT). No. of bitstreams: 1 gomes_aas_dr_bot_par.pdf: 53163720 bytes, checksum: 37484200626ab49924f0b9a1423b9c71 (MD5) Previous issue date: 2019-08-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Acidentes ofídicos são considerados um problema de saúde pública global, dada sua alta ocorrência de mortes, onde alguns casos resultam em sequelas irreparáveis, deixando o indivíduo desabilitado por toda a vida. Somente no Brasil, em média 20 mil mortes ao ano são registradas. Desta forma, alguns pesquisadores têm buscado estudar a estrutura-função de componentes dos venenos de serpentes peçonhentas à fim de desenvolver alternativas terapêuticas para esse problema de grande interesse médico. Um dos componentes que tem recebido atenção nas últimas décadas é a BthTX-I, uma proteína PLA2s-homóloga não catalítica, devido seu efeitos farmacológico notadamente miotóxico. Embora diversas técnicas tenham sido empregadas na compreensão do mecanismo de ação dessas proteínas, o conhecimento nessa área permanece controverso, tornando-se necessário a continuidade de estudos. O estudo estrutural e computacional de proteínas constitui uma alternativa viável para identificar as várias conformações de uma dada proteína, bem como seu comportamento dinâmico. Sendo assim, o presente trabalho buscou aplicar métodos computacionais, como simulação de MD, análise de Modos Normais (NM) e Dinâmica Molecular excitada por Modos Normais (MDeNM) à BthTX-I em pH ácido ou básico e nativa ou em complexo com o α-tocoferol – molécula tida como ativadora alostérica – na descrição do seu espaço conformacional, buscando compreender os aspectos estruturais do seu mecanismo de ação. Além disso, foram empregadas técnicas em solução, como Espalhamento de Luz Dinâmico (DLS), a fim de compreender o estado oligomérico da proteína frente ao α-tocoferol. Os resultados de MD mostraram que a BthTX-I possui estabilidade dimérica em pH neutro/básico. Já os experimentos de MDeNM mostraram que esta técnica é mais eficiente que a MD para descrever o espaço conformacional da BthTX-I, especialmente quando movimentos de alta amplitude são desejados, graças à sua combinação com os modos normais, causando altas alterações conformacionais do sítio de Ruptura de Membrana (MDiS), sendo exposto para o solvente e se aproximando do plano de sulfato que mimetiza a membrana celular. Tal movimento é altamente relacionado com a descrição dos ângulos de Euler, sugerindo que a exposição do MDiS é resultado de alterações da estrutura quaternária da BthTX-I. A liberdade do MDiS pode ser explicada pela perturbação da sua interação com a Hélice-I da BthTX-I causada pela presença do α-tocoferol, definindo assim uma característica importante para um ativador alostérico. Por fim, os experimentos de DLS reforçaram o caráter oligomerizante do α-tocoferol frente a BthTX-I, uma característica chave para a miotoxicidade dessa classe de proteínas. Ophidian accidents constitute a global public health problem due its high mortality, with some cases leading to permanent sequels. In Brazil, around 20 thousand deaths are registered. Therefore, researchers have been studying the snake venom composition in order to develop therapeutic alternatives to this medical problem. Some components from snake venom are highlighted in the past decades, as BthTX-I, a non-catalytic PLA2s-homologous protein, due its many pharmacological effects, notably myotoxic. Although many techniques have been employed to better understand the molecular mechanism of action for these proteins, this knowledge remains controversial, emphasizing the need to progress this field. The structural and computational study of proteins is a valuable tool to access the various conformations of a given protein, as well its dynamical behavior. Thus, the present work applied computational methods as MD, Normal Modes (NM) analysis and Molecular Dynamics with excited Normal Modes (MDeNM) to BthTX-I in acidic or basic pH and unbound or bound to α-tocopherol – a molecule identified as an allosteric activator – in order to describe the conformational space of this protein and determine the structural aspects of its mechanism of action. Further, biophysical experiments as Dynamic Light Scattering (DLS) were employed in order to comprehend the oligomeric form of BthTX-I with or without α-tocopherol. MD simulations showed that dimeric form of BthTX-I is stable when in neutral/basic pH conditions. MDeNM showed as a better tool to describe the conformational space of BthTX-I, specially when high amplitude movements are desired, due its mixing with normal modes, leading to high conformational changes of the Membrane-Disruptin site (MDiS), which were exposed to the solvent and approximated to the sulphate plane that mimics the cell membrane surface. This movement is highly related with the Euler angle description, suggesting that the MDiS exposure is result of quaternary movements of BthTX-I. The liberty of MDiS might be explained due the perturbation of its interaction with Helix-I of the protein caused by the presence α-tocopherol, describing an important feature that defines an allosteric activator. Furthermore, DLS experiments reinforced the ability of α-tocopherol to induce the BthTX-I oligomerization, a key property for myotoxicity for this class of proteins. CAPES: 001
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- 2019
6. Aminoguanidine hydrazones (AGH's) as modulators of norfloxacin resistance in Staphylococcus aureus that overexpress NorA efflux pump
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Dantas, Natalina, primary, de Aquino, Thiago Mendonça, additional, de Araújo-Júnior, João Xavier, additional, da Silva-Júnior, Edeildo, additional, Gomes, Ednaldo Almeida, additional, Gomes, Antoniel Augusto Severo, additional, Siqueira-Júnior, José Pinto, additional, and Mendonça Junior, Francisco Jaime Bezerra, additional
- Published
- 2018
- Full Text
- View/download PDF
7. Estudo computacional dos efeitos farmacológicos das miotoxinas Lys49 de serpentes (Familia:Viperidae): modelos moleculares para citotoxidade e miotoxidade
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Gomes, Antoniel Augusto Severo and Delatorre, Plinio
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Dockings moleculares ,Citotoxicidade ,Miotoxinas Lys49 ,Cytotoxicity ,Molecular docking ,Miotoxicidade ,Lys49 myotoxins ,Myotoxicity ,VEGFR-II ,BIOLOGIA GERAL [CIENCIAS BIOLOGICAS] - Abstract
Snakebites are and global endemic problem and the study of its components is important to understand and prevent them. Among its components, phospholipase A2 have been strongly studies as Lys49 myotoxins. However, understanding the molecular mechanisms of its pharmacological effects remains controversial until now. This work studied the Lys49 myotoxins pharmacological structural determinants, emphasizing cytotoxic and myotoxic effects. Protein sequence analysis as well as molecular docking with myotoxin Bn IV and VEGFR-II receptor and different anionic molecules, such as phosphate, heparin and lipopolysaccharide were performed. Sequence analyses showed defied regions within Lys49 myotoxins group, especially cationic regions. In accordance with this, molecular dockings performed in this work observed the presence of anionic non-specific sites, also a heparin recognition site. Molecular dockings between myotoxin Bn IV and VEGFR-II were satisfactory and indicated C-terminal tail as an important interactive region. Our results determine cationic regions as important for cytotoxic effects and bring a new molecular approach to the myotoxic effects, via VEGFR-II. In additional, molecular cytotoxic and myotoxic models for myotoxic Lys49 were presented Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES Acidentes ofídicos constituem um problema endêmico global, e o estudo de seus componentes é importante para compreender e preveni-los. Dentre seus componentes, fosfolipases A2 têm sido fortemente estudadas, bem como as miotoxinas Lys49. Contudo, o entendimento dos mecanismos moleculares que promovem seus efeitos farmacológicos permanece controverso até hoje. O presente trabalho buscou estudar os determinantes estruturais dos efeitos farmacológicos das miotoxinas Lys49, enfaticamente seus efeitos citotóxicos e miotóxicos. Foram realizados testes de análise de sequências entre tais proteínas, bem como dockings moleculares entre a miotoxina Bn IV e o VEGFR-II e diferentes moléculas aniônicas, como fosfato, heparina e lipopolissacarídeo. As análises das sequências apresentaram regiões bem definidas dentro do grupo das miotoxinas Lys49, notadamente regiões catiônicas. Em concordância com isto, os dockings moleculares realizados neste trabalho apontam para a presença de um sítio não-específico para cargas aniônicas, bem como um sítio de reconhecimento para heparina. Já os dockings moleculares entre a miotoxina Bn IV e o VEGFR-II foram satisfatórias e apontaram a cauda C-terminal como uma importante região de interação. Tais resultados determinam regiões catiônicas importantes para a realização dos efeitos citotóxicos, através do reconhecimento de fosfolipídios aniônicos, e trazem uma nova abordagem molecular para os efeitos miotóxicos, via VEGFR-II. Além disso, são apresentados modelos moleculares para os efeitos citotóxicos e miotóxicos das miotoxinas Lys49
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- 2014
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